Differences in the incidence and severity of musculoskeletal diseases, conditions, and sports injuries between males and females are the result of inherent anatomic, biomechanical, hormonal, and cellular/molecular differences. Responses to therapy (e.g., surgery, anesthesia, pain medication, pharmaceuticals, and rehabilitation) also differ by sex, but the mechanisms involved have not been well described, nor have they been correlated with clinical observations or disseminated to clinical audiences. For example, the majority of osteoporosis patients are female, and the majority of disorders caused by trauma or sports injuries occur in males. Much of the research on therapies for musculoskeletal disorders has involved the use of young adult animals, and for a number of experimental reasons, these animals have been female in the case of osteoporosis and male in the case of therapeutics. As a result, our understanding of these conditions as they present throughout life, and for the other sex, is limited. The 2014 AAOS/CORR/ORS/CMH-UCD Musculoskeletal Sex Differences Throughout the Lifespan research symposium and subsequent publication will bring basic scientists and engineers together with clinicians who treat the musculoskeletal patient at all stages of care to discuss advances in the understanding of how sex differences in biomechanics, biology and physiology impact musculoskeletal health and patient outcomes in order to identify new areas of research related to sex and gender issues over the entire lifecycle. The symposium will include presentations by leaders in their respective fields addressing the current state of the art, followed by group discussions to identify knowledge gaps and identify future research directions.